Metformin Treats Animal Model of Multiple Sclerosis

Finding new uses of existing medications is a field of great interest to biotechnology and pharmaceutical companies since it saves all the money needed for performing pharmacological and safety studies.  A recent example of a “new use for an old drug” comes to us from a study recently published from the Medical University of South Carolina. 

In the study (Nath et al. Metformin attenuated the autoimmune disease of the central nervous system in animal models of multiple sclerosis. J Immunol 2009 Jun 15;182(12):8005-14) the investigators treated mice bearing an MS-like disease called experimental allergic encephalomyelitis (EAE) with the drug metformin. 

Metformin is the most widely used drug to treat type 2 diabetics in the US.  It originates from the plant called the French Liliac, which was used for centuries in traditional medicine to treat diabetes associated with obesity.

Mechanistically Metformin works through inhibiting sugar production from the liver, a process called gluconeogenesis, which is much higher in type 2 diabetics as compared to non-diabetic patients.  It does this by activating an enzyme called AMPK

In the study it was found that administration of metformin suppresses symptoms of the MS-like mouse disease through decreasing entry of T cells and monocytes into the central nervous system of the animals.  Additionally, a suppression of inflammatory products such as TNF-alpha, IL-17, IFN-gamma was also observed.

The same enzyme, AMPK, which metformin activates in the liver, when activated in macrophages results in their loss of ability to cause substantial inflammation.

Obviously more research needs to be performed to see if the concentrations achievable in animals can be achieved at a stable enough level in humans without causing adverse effects.  However, besides practical implications of the study, the study is important because it teaches that activation of AMPK can lead to suppression of macrophage inflammatory mediator production.  This could lead to development of new classes of AMPK activators that are selectively designed for macrophage suppress.

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